Center of Excellence in Molecular Biology and Regenerative Medicine, Department of Biochemistry, JSS Medical College, JSS Academy of Higher Education & Research, Mysuru, India.
Department of Cardiology, JSS Medical College, JSS Academy of Higher Education & Research, Mysuru, India.
Indian Heart J. 2023 Sep-Oct;75(5):343-346. doi: 10.1016/j.ihj.2023.05.005. Epub 2023 May 20.
It is essential to investigate the prevalence of CYP2C19 alleles that affect drug metabolism. This study measures the allelic and genotypic frequencies of CYP2C19 loss-of-function (LoF) alleles CYP2C19∗2, CYP2C19∗3, and gain-of-function (GoF) alleles CYP2C19∗17 in the general population.
The study involved 300 healthy subjects between the ages of 18 and 85 recruited by simple random sampling. Allele-specific touchdown PCR was employed to identify the various alleles. The genotype and allele frequencies were calculated and checked for Hardy-Weinberg equilibrium. The phenotypic prediction of ultra-rapid metabolizer (UM = ∗17/∗17), extensive metabolizer (EM = ∗1/∗17, ∗1/∗1), intermediate metabolizer (IM = ∗1/∗2, ∗1/∗3, ∗2/∗17) and poor metabolizer (PM = ∗2/∗2, ∗2/∗3, ∗3/∗3) was made based on their genotype.
The allele frequency of CYP2C19∗2, CYP2C19∗3, and CYP2C19∗17 was 0.365, 0.0033, and 0.18, respectively. The IM phenotype predominated with an overall frequency of 46.67%, including 101 subjects with ∗1/∗2, two subjects with ∗1/∗3, and 37 subjects with ∗2/∗17 genotype. This was followed by EM phenotype with an overall frequency of 35%, including 35 subjects with ∗1/∗17 and 70 subjects with ∗1/∗1 genotype. PM phenotype had an overall frequency of 12.67%, including 38 subjects with ∗2/∗2 genotype, and UM phenotype had an overall frequency of 5.67%, including 17 subjects with ∗17/∗17 genotype.
Given the high allelic frequency of PM in the study population, a pre-treatment test to identify the individual's genotype may be recommended to decide the dosage, monitor the drug response, and avoid adverse drug reactions.
研究影响药物代谢的 CYP2C19 等位基因的流行情况至关重要。本研究旨在测量一般人群中 CYP2C19 失活（LoF）等位基因 CYP2C19∗2、CYP2C19∗3 和获得功能（GoF）等位基因 CYP2C19∗17 的等位基因和基因型频率。
本研究采用简单随机抽样的方法，招募了 300 名年龄在 18 至 85 岁之间的健康受试者。采用等位基因特异性降落 PCR 来鉴定各种等位基因。计算基因型和等位基因频率，并检查 Hardy-Weinberg 平衡。根据基因型预测超快代谢者（UM = ∗17/∗17）、广泛代谢者（EM = ∗1/∗17、∗1/∗1）、中间代谢者（IM = ∗1/∗2、∗1/∗3、∗2/∗17）和弱代谢者（PM = ∗2/∗2、∗2/∗3、∗3/∗3）。
CYP2C19∗2、CYP2C19∗3 和 CYP2C19∗17 的等位基因频率分别为 0.365、0.0033 和 0.18。IM 表型占主导地位，总体频率为 46.67%，其中 101 例为 ∗1/∗2，2 例为 ∗1/∗3，37 例为 ∗2/∗17 基因型。其次是 EM 表型，总体频率为 35%，其中 35 例为 ∗1/∗17，70 例为 ∗1/∗1 基因型。PM 表型的总体频率为 12.67%，其中 38 例为 ∗2/∗2 基因型，UM 表型的总体频率为 5.67%，其中 17 例为 ∗17/∗17 基因型。
鉴于研究人群中 PM 等位基因的高频率，建议在治疗前进行个体基因型检测，以确定剂量、监测药物反应并避免药物不良反应。
